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Muscoloskeletal Diseases #8
Infections and Tumors Professor Scotti 21 January 2014 Author
Francesca Rossetti Reviewer Luigi Bonini
INFECTIONS Infections in orthopedics are osteomyelitis,
arthritis and infected arthroplasty.
OSTEOMYELITIS Osteomyelitis is an infection of bone and bone
marrow; it may be caused by
direct inoculation of bacteria through an open fracture or via
the hematogenous route by blood-borne organisms. Osteomyelitis is
typically caused by bacteria, very rarely by fungi. It may be acute
or chronic.
ACUTE HEMATOGENOUS OSTEOMYELITIS is typical of children and is
diagnosed within 2 weeks from the onset of symptoms; typically
patients seek for medical advice within 48 hrs since symptoms are
very severe. It shows me-ta-epiphyseal localization (lower
extremity more frequent) and it is typically monosthotic, i.e. it
affects only one bone.
The metaphysis is the typical localization in children because
it is highly vascularized. This area is very metabolically active
because of the presence of the growth plate allowing for limb
lengthening during childhood and adoles-cence; this area is
extremely vascularized and that's why typically hematog-enous
bacteria stop here. Moreover, the growth plate, which is avascular
and cartilaginous, is a natural barrier to the diffusion of the
abscess to the epiphy-sis (you can appreciate it also in the MRI
below). So, generally the onset of acute hematogenous osteomyelitis
is located here in the metaphysis with no spread to the epiphysis;
this may, however, occur in more advanced cases.
As you can see here in this drawing (left), the ab-scess
diffuses prevalently through the bone and tends to elevate the
periosteum. This causes abnormal ossifi-cation around the bone: the
cambial layer of the perios-teum in fact is rich in mesenchymal
progenitor cells which typically participate in bone healing; in
this case these cells are stimulated by the inflammatory
microen-vironment rich in cytokines, so the periosteum tends to
ossify during osteomyelitis.
Here (below) you can see how the infectious pro-cess may also
erode the periosteum and go through the soft tissue and the skin,
forming a draining sinus.
Q: How long does this take to develop? A: It's variable, but
this doesn't happen in the first days. Typically it's difficult
to see this nowadays. If it's superficial e.g. in the distal
metaphysis of the tibia, it may take a few days. The progression of
osteomyelitis is quite fast also because the immune system of
children is not completely mature so these kinds of infec-tion tend
to be more aggressive in kids.
Symptoms include pain, loss of limb function, limp (they cannot
walk), swell-ing (can be very important), tenderness, soft tissue
abscess (in case of diffusion of the infection to the soft
tissues), and fever (up to 39-40 C). Typical presenta-tion is
within 48 hrs.
The most sensitive monitor for diagnosis and follow-up is
C-reactive protein, while MRI is the most sensitive and specific
imaging technique for diagnosis and differential diagnosis.
Differential diagnosis is crucial in children presenting with
typical symptoms; acute hematogenous osteomyelitis' symptoms are in
fact very similar to those of sarcoma (Ewing Sarcoma), that's why
it's vital to perform an adequate diagnosis in both cases. Bone
scan may also be very useful when diagnosis is unclear.
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The two following imaging features are characteris-tic of
osteomyelitis and may help you in the DD with e.g. sarcoma: the
sequestrum (ita: sequestro) and the involucrum (ita: sarcofago).
Sequestra are areas of dead bone with surrounding granulation (see
on the MRI on the left) while the involucrum is the periosteal new
bone formation (appears later wrt sequestra) (in the MRI the
periosteal membrane appears enhanced and detached by the infection
and ossified because of the activation of cells).
Clinical case: 9 yo female after 7 days of pain; so quite a
delayed diagnosis. Look at the X-ray pictures and this patchy bone
resorption, there is not a clear ar-ea of resorption, but it's
rather patchy. You can see here how the growth plate has been
interrupted and, since the diagnosis has been delayed, also the
epiphy-sis has been involved. So these are the consequences of a
delayed diagnosis and that's why it's crucial to do it ASAP. What
could be the consequences of diffusion to the epiphysis? Possible
complications can be osteoar-thritis and infection to the joint
with very severe conse-quences, e.g. disruption of the cartilage,
necrosis, and early osteoarthritis. Since this was a young child,
this pathology may affect the normal growth pattern. You may have
both necrosis, so a growth arrest, or you may have a stimulation of
cells, so excessive growth compared to the controlateral side. But
this is difficult to predict and it also depends on how soon you
treat the osteomyelitis.
Treatment is based on identification of pathogen involved, by
performing blood culture and with local aspiration if possible.
Often also surgical debridement is required, especially in case of
massive infection. However, while you're waiting for cultures
(typically you wait 5 days) you can establish an empirical therapy
with the most common antibiotics vs common bacteria, as you know
that most of these infections in children are due to S. Aureus
(most important), but also gram-bacilli and group B Streptococci in
the newborn, while in children >4yo group A strepto-cocci. In
adults there is a wide variety of bacteria, but still S.Aureus is
the one most commonly involved.
ACUTE POST TRAUMATIC OSTEOMYELITIS is typical of adults. Usually
it is secondary to open fractures,
that's why prevention, adequate prophylaxis of open fractures is
very important and its usually done with a com-mon antibiotic; open
fractures with wide soft tissue damage (e.g. type III of Gustilo
Anderson class.) require a mul-tiple antibiotic therapy in order to
cover gram-, gram+ and anaerobes. Clinical findings are very
similar to those of the hematogenous, as this is again an acute
osteomyelitis. The most common infecting pathogens are S. Aureus
(because it resides on the skin), P. Aeruginosa (quite aggressive,
infections can be quite troublesome), and gram- bacteria. Empirical
therapy again should be started immediately while waiting for
cultures.
In case of fractures which became infected after implantation of
any kind of hardware (plates or nails), you have to remove the
hardware because this may be a site where bacteria attach and in
which it is difficult to kill them with the antibiotic. So we
always have to use an external fixator to minimize the implants at
the site of infection.
This drawing shows the osteomyelitis with all the bacteria
growing across the bone; you perform surgical deb-ridement to clean
it up, remove the necrotic bone and use an external fixator as a
stabilization device: as you can see, it does not include any kind
of implant through the infection site. Finally, you properly cover
with soft tissue, so you have to perform a muscle flap if needed.
This should be accompanied by a proper use of antibiotics, i.e.
intravenous antibiotics at high doses.
CHRONIC OSTEOMYELITIS is typically the re-
sult of a poorly treated acute osteomyelitis, usually
post-traumatic. We don't see chronic osteomyelitis in children,
because symptoms are so severe that they have diagnosis soon and
you can establish a proper and effective therapy in time. In adults
this is different: especially after a trauma, onset of os-
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teomyelitis may be very subtle, not as severe as in children and
that's why it may become chronic.
Risk factors include local/mild systemic deficiency, smoke,
major nutritional systemic disorders (e.g. diabetes), diabetic foot
(skin ulcers if not treated may involve the bone). Typical patients
are old, diabetic or immunosup-pressed for any reason (e.g.
systemic disease, age...) or IV drug abusers (because they have a
continuous source of bacteria from the skin).
Typical infecting organisms are S.Aureus and P.Aeruginosa, but
now you have to be very careful to the methicillin-resistant
S.Aureus (MRSA): this is an emerging clinical problem because it
can be treated with only very few antibiotics, vancomycin for
example.
This is the Cyernys Anatomic classification of chronic
osteomyelitis, very academic:
Medullary Superficial Localized Diffuse The natural history is
quite typical: periods of quiescence (with no big symp-
toms) and periods of exacerbation. This is why they seek medical
advice quite late, because they have long periods of quiescence,
they may take some NSAIDs dur-ing the exacerbation periods, so they
can only get worse.
There is no rationale for empirical therapy in chronic
osteomyelitis: they are of-ten not given any antibiotic at all for
months, so it doesn't make any sense to estab-lish an empirical
antibiotic therapy. Therapy is only based on deep cultures; even
blood cultures are not often diagnostic in these patients. You have
to go in the infection site, perform a biopsy, do a debridement of
the lesion and ask for cultures.
ARTHRITIS This is another very important topic which can have
terrible consequences if not treated.
Here you can see the typical presentation: a knee like this
should always warn you: here there is some-thing wrong and whatever
it is, it must be serious.
CHILDREN: causes are hematogenous spread from metaphyseal
osteomyelitis or from other infection sites, or it can be a
complication of therapeutic/diagnostic procedures. So, every time
you perform an intraarticu-lar procedure (like steroid injections)
you have to be very careful with abscesses. Even arthroscopy, a
very minimally invasive surgical procedure, may have arthri-tis as
a consequence.
An important organism you have to consider is haemophilus
influenzae (30% of < 5 yo patients), plus S.Aureus and type A
streptococci. The most common site is the hip; then proximal
humerus, distant fibula, radial neck. Usually it involves one
single joint.
Treatment: surgical decompression and drainage: you have to
decompress the intraarticular swelling, because it may result in
necrosis. Also, you have to immediately establish an empirical
therapy while waiting for definitive cultures.
Terrible consequences can ensue if not treated properly. Here
you can see an intraarticular abscess which can cause damage to the
vascular supply especially at sites like the hip where
vascularization is not particularly well represented: the femoral
epiphysis has been completely disrupted because of the
intraarticular pressure. In these cases antibiotic treatment alone
is not enough and surgery to decompress the joint is mandatory.
In ADULTS arthritis is more commonly a complication of
therapeutic/diagnostic procedures (iatrogenic), or less commonly
form hematogenous spread. The most common infecting organisms are
S.Aureus, N. Gonorrhoeae and streptococci.
Treatment is the same: first empirical therapy plus definitive
cultures. It is im-
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portant to perform decompression which can be arthroscopic:
basically you do an arthroscopy, wash the joint (you do arthroscopy
under fluid, so you can wash it) you can also leave one tube going
into the joint, one tube going out in order to continuously wash
the joint even in the ward for a couple of days and decompress.
What I want you to know is that the sequelae may be terrible. An
arthritic joint may develop, rapidly evolving to osteoarthritis and
also muscle contraction complicates the situation. So every time
you see a knee like this in an adult or in a child, it's crucial to
start treatment ASAP, even when you are in the ER: give immediately
an antibiotic after performing an ar-throcentesis, a synovial fluid
aspiration, not to have false negatives. If you are seeking for the
bacteria responsible for the infection you want to harvest the
fluid or the tissue when the patient is not taking any an-tibiotic,
otherwise the bacterial count would be too low.
These are the consequences of an improper or of a proper but
late treatment. Look at the disruption: the patient had to receive
prosthesis of the good hip because of arthritis.
INFECTED ARTHROPLASTY As I said we are implanting every year
more and more arthroplasties. Metallic implants, as in the case of
heart
valves, are very prone to infection, and when they get infected,
this is really a devastating complication for the patient. It
causes severe disability requiring long term IV antibiotic therapy
and a two stage surgical procedure: you have to first remove the
implant (which is infected, it is impossible to clean it from the
bacteria with antibiotics), im-plant a cemented spacer (a kind of
prosthesis made of cement capable of releasing locally antibiotics
in order to sterilize the area), and then after months during which
the patient cannot walk on his limb (the cement spacer doesn't work
like a prosthesis), you can implant a new prosthesis.
Infection to an arthroplasty can occur at any time after
surgery. That's why, even if the risk is higher in close proximity
to surgery (1st six weeks), sometimes infections in the mouth,
teeth, lungs, urinary tract, or skin, or just after regular dental
procedures that involve gum bleeding can force bacteria in the
bloodstream, causing infected arthroplasty. Therefore you always
have to recommend antibiotic prophylaxis to any patient carrying a
pros-thesis before any (even dental) surgery. Every time we operate
a patient, in case we do a medium/demanding surgery, we always
establish a prophylactic therapy, which is very effective in
minimizing the risk. However, 1-1.2% of patients receiving an
arthroplasty get infected, despite the prophylaxis. This is a
complication you are going to see if you are attending an
orthopedic department. In our department we do maybe 120 prostheses
per year, so we see at least one infection in these patients,
whatever we do to prevent it. These are part of the complications
which are not caused by malpractice, but by the procedure itself.
What you can do is to recommend to patient to establish prophylaxis
and of course never operate on patients who have an ongoing UTI or
dental infection.
The most frequent pathogens are Staphylococcus Epidermidis and
S.Aureus, which are on the skin, group B streptococci and of course
MRSA; MRSA infection to an arthroplasty is a really severe
condition because it requires long-term therapy with multiple
antibiotics with frequently lots of complications.
This is the early presentation of an infected total knee (here
in a recently operated patient). The joint is typically swollen,
red and warm. The joint is typically flexed in a po-sition as
motion is usually very painful, so we have loss of function, and
also drainage may be present.
CRP is typically very elevated before starting the antibiotic
therapy and is the best monitor to assess the effectiveness of your
therapy. If your antibiotic is the right one and it is effective,
CRP decreases fast once you have started the treatment.
Q: How do you distinguish if CRP is elevated due to surgery or
due to infection? A: CRP is increased after surgery, but not that
much compared to how it can be increased in such cases; so
with such infections CRP is much more increased. Also, it
generally decreases in the first days after surgery, so within the
first six weeks you have time to establish the proper diagnosis
based on CRP elevation, fever and symp-toms. Moreover patients
usually have fever after surgery, because surgery is a trauma,
patients are reabsorbing the hematoma which is rich in cytokines
and this causes fever. Fever in the first days after surgery is a
very unspe-cific sign, it is not a sign of infection. It has to be
correlated with elevated CRP and it has to be prolonged for days
after surgery. The value depends on the unit used by the lab: in
our lab, after surgery we may have a value of CRP of 10/20/50 while
with an infection is really much higher like 100.
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Infection of prosthesis causes its mobilization. There are some
very specific radiological signs that can help you in performing
diagnosis (image on the right). Look at this tibial plate that has
been mobilized. All the bone around here has been resorbed because
infection activates macrophages and osteoclasts which resorb the
bone around the prosthesis; it is very painful because this is
moving, it is not stable anymore. This pa-tient had to be treated
with revision implant, bone grafting...a very long treatment.
Q: What is the resolution rate of these infec-tions?
A: I don't really have statistical values, but in the normal
population it is close to 100%. Chronic infections are rare.
Typically they occur in immun-ocompromised patients.
TUMORS
Musculoskeletal oncology is a very complex topic which is 100%
managed by orthopedic surgeons specialized in musculoskeletal
oncology.
Tumors to the bones are very rare and account for ~2% of all
malignant tumors, while metastatic bone dis-eases are probably the
most common form of metastasis. Bone metastases are an emerging
clinical problem which requires proper treatment.
Grading means "how bad is the tumor". Grading is based on
histopathological features, so it's only given on the basis of
biopsy, not on imaging. Sarcoma is the general name for mesenchymal
tumors. Grade 1: very well differentiated tumors resembling the
original tissue, with very low risk of metastasis Grade 2 Grade 3:
poorly differentiated, very high risk of metastasis. However,
grading of sarcomas is typically very difficult for the
pathologist. So, they tend to classify them into
high grade and low grade, i.e. poorly vs highly
differentiated.
The TNM classification of tumors is a bit different here. The
tumor size is not calculated in cm, but is instead based on the
diffusion of the tumor through a compartment; the T of sarcomas is
defined as intracompartmental (T1) vs extracompartmental (T2), i.e.
wheth-er the primary tumor of the bone extends out of the bone or a
soft tissue sarcoma extends out of the fascia. This is based on
imaging studies not on biopsy like the M, so whether it is
metastatic or not. That's why every time you suspect a malignant
tumor, always ask for a total body CT scan and a bone CT scan.
Enneking's staging system is based on grade (G), tumor site (T) and
metastatic status (M). It identifies three stages, 1, 2 and 3,
which correspond to low grade, high grade without metastasis and
high grade with metastasis. Also, stages 1 and 2 are further
divided into a and b according to their site, whether they are
compartmental or not. Typically a low grade sarcoma does not
determine metastasis at dis-tant sites but it may.
Q: What about the N staging? A: Lymph node involvement is
extremely UNfrequent in sar-
comas. Only some subtypes, e.g. synovial sarcomas, give
metas-tasis to lymphnodes.
Localization is crucial and follows typical patterns
according
to age of patient and tumor type. You don't have to memorize
this, but it's to give you an idea. Of course you have to memorize
the sites of tumors, but we'll talk about it later; I want you to
un-derstand how difficult it may be to perform diagnosis on the
basis of an X-ray when most of them look the same on the X-ray. But
if you know the features, then diagnosis is easier. Here you can
see the localization 30 yo. Metastasis and myeloma or lymphoma
typically can involve the diaphysis, myeloma being a tumor of
adults, while Edwing sarcoma is a tumor of children,
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but still localized in the diaphysis. Epiphysis is typically
spared by tumors because of the barrier represented by the growth
plate; however, chondroblastoma, for example, or infections can
affect it; the growth plate is also typically disrupted by
malignant tumors, like osteosarcomas. The metaphyseal area can be a
site of many tumors. Giant cell tumor is typically epiphyseal,
while cartilage tumors, chondrosarcomas, are metaphyseal.
Benign tumors of bone are also very common but we don't know the
epidemiology because, being asymp-tomatic, their diagnosis is
typically incidental. So anyone may have a bone cyst. Lots of
patients are diagnosed when they fall down and they may have
fractures for a minimal trauma because the bone was weakened by the
cyst or the enchondroma for example; this is typical of
enchondromas of finger. Benign tumors are innocuous, but have this
feature, they cause pathologic fractures.
Typical symptoms of malignant tumors are persistent pain and
progressive swelling, so the symptoms typi-cally should drive the
patient to seek medical advice immediately because they are quite
scaring, but especially soft tissue sarcomas tend to grow very
slowly and especially old patients don't really care about it. They
affect mainly young patients.
Surgical resection is the mainstay of treatment; you always have
to remove the tumor. These tumors are never treated with CT/RT
only, you have to perform resection. Neoadjuvant/adjuvant CT and/or
RT depending on the tumor type and grade have to be performed.
Resection can be performed in different fashions:
Intralesional resection: improper treatment for a malignant
tumor. Marginal resection: you only enucleate the tumor. This is
not a proper treatment for a malignant tumor while
it is a proper treatment for benign tumors. Wide resection: with
wide margins in healthy tissue around the tumor. It is a proper
treatment for some ma-
lignant tumors Compartmental/radical resection: we take out the
entire compartment surrounding the tumor. It is a proper
treatment for high grade malignant tumors. Compartmental
resection is very important be-cause you often have
skip-metastases: these are metastases to the same tissue, but
distant-ly from the primary tumor. Skip metastases may be
microscopic and that's why you should perform a wide resection.
Also, these tumors diffuse through the vessels, not through the
lymphatics, that's why diffusion is typically lo-cally, or to the
lungs or to the bone. Now we start our overview of tumors, starting
form conditions which are not tumors.
TUMOR-LIKE CONDITIONS NON-OSSIFYING FIBROMA: it is not a tumor.
This is the typi-
cal presentation in the metaphysis. Typically you see a
radiolucent lesion like a cyst surrounded by a sclerotic rim. The
sclerotic rim is always a sign of a benign lesion; malignant tumors
do not show this sclerotic rim.
They often resolve spontaneously; so often no treatment is
re-quired when the risk of pathological fracture is low, whereas it
is required if the lesion is big and there's risk of pathologic
fracture. In this case the patient needs no treatment, as it is not
that big.
Fibroma typically does not disrupt the corti-ces of bone, so
they make the bone weaker compared to other kinds of lesion. This
is the typical incidental finding of patients that may come to the
ER: they will be very scared, but you can reassure them because it
is not serious, nothing really pathologic.
Another tumor-like condition is the SIMPLE
BONE CYST. The difference with fibroma is that, as you can see
here in the MRI (central), cysts are filled with fluid.
Simple bone cysts are characterized by symmetric expansion with
thinning of the cortices. So, pathologic frac-
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tures may occur more frequently in cysts wrt fibromas.
Very common presentation with a fracture, otherwise they are
totally asymptomatic. They show metaphyseal localization (proximal
femur, humerus and distant fibula): it may extend to the epiphysis
or the diaphysis, but it starts in the metaphysis.
Treatment is mandatory, since the risk of pathologic fractures
is very high. Treatment is curettage (i.e. intrale-sional
resection) and bone grafting (not always performed, only for big
cysts). Bone grafting may be autologous from the iliac crest, or
you can use synthetic bone substitutes hydroxyapatite or allografts
from multiorgan donors.
Musculoskeletal transplants are the most frequently preformed
transplants. We very often use allografts taken from multiorgan
donors for ligament reconstruction, bone grafting procedures. And
we have no rejection, since the-se allografts are decellularized,
so there are no allogeneic cells, it is exclusively extra cellular
matrix.
ANEURYSMAL BONE CYST (ABC): this is not a tumor, but it is
typically really disrupting. Patients are typically
young (
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affecting also the cartilage.
It is uncommon in children and adolescents, it is more typical
of adults 30 - 50 yo. It involves typically epiphysis and
metaphysis of long bones (50% around the knee and 10% distal
radius).
Treatment is very difficult and has to be planned cor-rectly.
Treatment is curettage (removal of all the tissue inside which is
brownish and soft) in combination with lo-cal adjuvants (cement,
phenol), to kill all the possible remaining cells. However,
depending on the patient, you may also decide to do a bone grafting
or even a massive allograft, i.e. implanting a whole piece of bone
from a ca-daver or to implant a prosthesis. So treatment is very
challenging and depends on the site. I remember a patient with
giant cell tumor to the distal tibia with the involvement of the
ankle joint with subchondral bone, so all the carti-lage. Even if
we were very conservative with the treatment, he developed late
osteoarthritis. There was no func-tional cartilage in the joint
anymore.
Q: Is it fast or slowly progressing? A: This is very difficult
to say, because, since it is asymptomatic patients come to you only
when pain and dis-
ruption come up, so you never know when it started, you only
know when it's like this.
ENCHONDROMA: this is a very common cartilaginous bone tumor.
They are persisting islands of cartilage in bone developed through
endochondral ossification, like the tibia. Hyaline cartilage has
some degree of calcification. This is only cartilage not completely
calci-fied and this is a pathological fracture; typical fracture of
the proximal phalanx after a minimal trauma. They're seen at any
age especially because they are totally asymptomatic, so diagnosis
is typically inci-dental because of pathologic fractures mostly or
dur-ing routine X-rays maybe for minor trauma.
Treatment is curettage, so you just take it out.
OSTEOCHONDROMA (EXOSTOSIS): it is another typical cartilaginous
tumor. They are small overgrowth of cartilage at the edge of a
growth plate that develops into a bony protuber-ance with a
cartilaginous cap. This was the growth plate and because of an
anomaly, there is an overgrowth. They can have a pedicle-like
appearance or the can be sessile, so with a very wide basis. Of
course at this site it may have some complications, like
compression of the neuromuscular bundle. Here is a patient with
brachial artery pseudoaneurysm because of an osteochondroma. Here
the bony protuberance has a cartilaginous cap: this is calcified
cartilage and this grew like a continuation of the growth
plate.
There is a small risk of malignant transformation, especially
when it's isolated. However, with multiple lesions the risk of
malignant transformation increases up to 6-fold: in those cases you
always have to perform strict follow up to check for malignant
transformation and to possibly remove these lesions even if they
are not symptomatic. They may be symptomatic when they compress
neurovascular structures or muscles, when they create swelling.
They affect typically teenagers. They grow together with the
growth plate, so they stop growing together with the bone: if the
growth continues after the closure of the growth plate, it is a
sign of malignancy. So when there is no growth plate like here, if
the osteochondroma continues to grow, that is a sign of malignancy.
Treatment is marginal resection. It is quite common in the distal
phalanges.
MALIGNANT BONE TUMORS CHONDROSARCOMA: this is a malignant tumor
of cartilaginous origin. Low grade chondrosarcoma may re-
semble an enchondroma, that's why you have to perform proper
imaging when you see something like this. In gen-eral, if you don't
have an orthopedic oncology background you always consider them
enchondromas; indeed most of them are just enchondromas but still
in some cases, especially when the borders are not well defined
like here, these lesions may be malignant. And that's why you
always have to be very careful.
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Chondrosarcoma is the most common primary ma-lignant tumor of
the bone. They are typically low-grade, so not particularly
aggressive. It affects the proximal long bones (proximal humerus,
proximal fe-mur) and it's frequently found around the knee (distal
femur, proximal tibia), pelvis and shoulder. Localization is
typically central and metaphyseal. It is painful and it can present
as an enlarging mass, like this one. This is a high grade
osteosarcoma: massive destruction of normal anatomy, huge mass
requiring wide/radical re-section.
Surgical treatment of this tumor may be difficult sometimes
because they are in close proximity with vascular structures: you
want to remove them properly, but preserving motion. We'll see
afterwards that most malignant tu-mors were once treated with
amputation. Of course this is not true anymore; we always try to
perform limb-saving procedures by using allografts and prostheses.
Since chondrosarcomas are mainly or typically low grade, they do
not require neoadjuvant or adjuvant chemotherapy, only surgery or
radiation therapy, in case you did not have clean margins. If you
did not an adequate surgery, you have to perform a radiation
therapy.
OSTEOSARCOMA: it is the second most common primary malignancy of
bone. There are many subtypes (that
you don't need to know); teleangectatic was one, the DD with
bone cyst.
Differently from chondrosarcoma, osteosarcoma is mainly
high-grade; so this is an extremely aggressive condi-tion. It is
typical of children, that's why you have to perform an adequate,
ASAP diagnosis. Usually localized about the knee (=distal femur or
proximal tib-ia) (50%) in children with a second peak in late
adulthood.
This (right) is the typical appear-ance of osteosarcoma: patchy
osteolyt-ic lesions, very wide alterations to nor-mal anatomy. It
can be barely visible, but one sign that may help you in the
diagnosis is the Codman triangle: it is a periosteal reaction to
the tumor. It is typically a sign of malignant bone tu-mor. Always
perform an MRI, since it is usually diagnostic (above you see that
the MRI could detect the edema and bone involvement that was not
visible on x-ray, in same patient). Also adults may be affected but
much less frequently.
These tumors are treated with neoadjuvant CT + wide/radical
resection and reconstructive procedure + adjuvant CT, a very
aggressive treatment. Chemo is not required in low grade, but low
grade osteosarcomas are rather rare. This is one of the most
important successes of polytherapy with 70% of long term survival.
All of these patients used to undergo amputation decades ago. Now
70% of these patients are long term cured with a limb sparing
procedure. Metastases are typically to the lung and to the
bone.
EWING SARCOMA: this is a terrible
condition, typically affecting young chil-dren >5 yo. Its
origin is unknown, we don't know from which cells it originates.
It's mainly located around the knee, proximal humerus, femoral
diaphysis and symp-toms are pain, mass, swelling, fever, ele-vated
erythrocytes sedimentation rate, anemia, leukocytosis; the
differential diag-nosis is with osteomyelitis, and since this is an
extremely aggressive malignant tu-mor, DD has to be performed
immediately, because the consequences of a delayed diagnosis both
of osteomyelitis or of Ewing sarcoma may really compromise the
success of treatment.
You often see a large disrupting mass. Disruption can be
enormous or minimal, but in a patient with these symptoms always
ask for an X-ray and full blood count. Treatment is the same of
osteosarcoma, plus radiation. So treatment is even more
aggressive.
Limb sparing surgery: standard of care. One of the most relevant
advances in surgery in the last decades, which has a strong impact
on the quality of life. We do not perform primary amputation
anymore in bone tumors,
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especially in children (like picture on the right, left image).
Nowadays we do use mod-ular prostheses (also taken from cadavers);
this is a total femur prosthesis (picture on the right, right
image). Function will not be optimal, but it is better than the
loss of a limb.
Allograft-prosthesis composite is a type of salvage surgery:
plastic surgeons can reproduce the extensor mechanism of the knee,
the quadriceps, by using a latis-simus dorsi flap. It can be
performed both in children and in adults.
I'll show you some examples. This (left) was a malignant tumor
we treated with a wide resection implanting a modular reversed
prosthesis; after this procedure the functionality of the limb was
not iden-tical to a normal limb, he won't play vol-leyball, but
still perfectly compatible with normal life.
This is another example of limb-sparing surgery, tumor to the
proximal tib-ial metaphysis: what we did was an allo-
graft prosthesis composite. So we implanted a prosthesis but
since we had to resect all the proximal tibia, we cut the tibia in
the diaphysis, we put here a massive allograft from a cadaver and
then put the prosthesis on the allograft. The benefit here of
having an allograft was that we had the possibility to at-tach the
patellar tendon to the tendon of the allograft allowing for some
func-tion. Without this allograft we would have to attach the
patellar tendon to the prosthesis which is metallic and does not
allow for the integration of the ten-don. So, no extension is
possible without an allograft. Again function here was very good:
patient could walk without crutches after wide resection.
SOFT TISSUE SARCOMA: sarcomas may arise also from soft tissues.
This is the typical presentation, a huge
mass growing within thigh. They don't feel it, especially
because the patients are usually old, with poor care of
themselves.
Soft tissue sarcomas may arise from fibrous, fatty, neural,
muscular, synovial, vascular tissues. Typical presen-tation is a
painful, or even painless, frequently enlarging mass.
By definition, every mass >5cm deep to fascia has to be
considered a sarcomas; even lipomas which are benign tumors of fat
may be larger than 5 cm. They have to be removed properly.
In children the most common is rhabdomyosar-coma, which is an
extremely aggressive tumor; oth-erwise they are typical of
adults.
Metastases are to the lungs or lymphatics in 5% of cases (only
in synovial sarcoma and rhabdomyo-sarcoma); so lymphatic metastases
are really uncommon in sarcomas.
Treatment is wide/radical resection in combination with adjuvant
therapy depending on the grade. Typically the very large masses are
low grade, because they develop slowly and they are painless.
METASTASES They are more common in adults. Metastases
typically
come from breast, lung, prostate, kidney, thyroid carci-nomas.
Common localizations are to the pelvis and to the spine, ribs and
proximal limbs (proximal femur, proximal humerus). The most
important problem with metastases is the risk of pathologic
fractures because they impair qual-ity of life. I don't want to go
into the details of metastatic mechanism of osteolysis; however I
want you to know that osteolysis is not caused by the cancer cells
directly. In-stead, tumor cells release PTH-related peptide that
stimu-
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lates cells towards an osteolytic phenotype; also, osteoclasts
are activated and secrete TGF- and IGF1, which fur-ther enhance the
release of PTH-rp. So this is basically a vicious circle of
metastatic bone disease and osteolysis continues and can only get
worse without treatment.
PATHOLOGIC FRACTURES These are a very important clinical entity
for you, since they will be more and more common because cancer
is
becoming a chronic disease. Most treatments of cancer result not
in a cure, but they make cancer chronic, increas-ing the risk of
bone metastasis.
The best treatment is prevention, so you have to be able to
evaluate impending fractures to understand whether a bone
metastasis may determine a fracture with minimal trauma. Typically
we perform a prophylactic in-ternal fixation of prosthetic
replacement when more than 50% of cortical destruction occurs or
50-75% of metaph-yseal destruction. The goal of this treatment is
not to cure the patient from cancer, but to maintain independence,
avoid fractures and control pain. Treatment has to be as definitive
as possible.
Commonly we use cement (PMMA) as an adjuvant. Here (first image
of the picture on the right) the metasta-sis was treated with
resection, cement and plate; we want this humerus to be strong to
allow the patient to live nor-mally. Here (second image) the
metastasis was in the femoral neck with disruption of structures,
so very high risk of pathologic fractures with implantation of
prosthesis.
Look at this (right) pathologic fracture: there is no bone here.
And look at this skip metastasis, very prob-lematic to treat: we
have to perform a resection, implanta-tion of a modular prosthesis
with a long stem and cement in order to allow for immediate weight
bearing and avoid relapse. This was an improper treatment: you
cannot use a plate without cement for a metastasis, otherwise the
metastasis continues to grow. What they should have done was to
resect the whole piece and implantation of a modular
prosthesis.
I want to show you another important concept that is very up to
date: isolated lesions 2 years after diagnosis of primary (possibly
with a good prognosis) disease have to be treated radically with
wide resection. You have to consider this kind of metastases like a
new primary to be treated radically because these patients have a
very long life expectancy. We made a massive allograft from a
cadaver donor so that we could attach the glutei here to the
greater trochanter and this was synthe-sized with a plate to the
normal bone. These patients live usu-ally 7-8 yrs after such a
treatment so a long survival after the metastasis. *hip
reconstruction video*